The objective of this research proposal is to explore the possibility that there is a circulating signal for a "control system" which regulates the long term stability of body weight. Evidence for such a signal has been reviewed. Some of the possible circulating factors which could provide this signal are discussed and the research plan is outlined with this background. If there is such a factor, it might be a steroid or it might be a peptide of protein. Other possible considerations are the circulating metabolites such as glucose, glycerol, fatty acids and amino acids. Hormonal signals might also play a role in such a system, particularly insulin. The research proposal which is developed plans to utilize the system of parabiosis to study this problem in detail.